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Eur J Pharmacol. 2020 Jan 15;867:172837. doi: 10.1016/j.ejphar.2019.172837. Epub 2019 Dec 5.

Assessment of cancer stem cell marker expression in primary head and neck squamous cell carcinoma shows prognostic value for aldehyde dehydrogenase (ALDH1A1).

Author information

1
Department of Otolaryngology, Faculty of Medicine and Dentistry, Medical University of Warsaw, Stępińska 19/25 Str., 00-739, Warsaw, Poland. Electronic address: szafarowski.t@gmail.com.
2
Department of Medical Informatics and Telemedicine, Medical University of Warsaw, Litewska 14/16 Str., 00-581, Warsaw, Poland. Electronic address: jsierdzinski@wum.edu.pl.
3
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA; UPMC Hillman Cancer Center, Pittsburgh, PA, 15213, USA. Electronic address: ludwign@upmc.edu.
4
Department of Biochemistry, First Faculty of Medicine, Medical University of Warsaw, Banacha 1 Str., 02-097, Warsaw, Poland. Electronic address: alicja.gluszko@wum.edu.pl.
5
Department of Biosensors and Processing of Biomedical Signals, Silesian University of Technology, Roosevelta 40 Str., 41-800, Zabrze, Poland. Electronic address: anna.filipowska@polsl.pl.
6
Department of Biochemistry, First Faculty of Medicine, Medical University of Warsaw, Banacha 1 Str., 02-097, Warsaw, Poland. Electronic address: mszczepanski@wum.edu.pl.

Abstract

Cancer stem cells (CSCs) play a key role in carcinogenesis and progression of head and neck squamous cell carcinomas (HNSCC). The most common markers indicating for CSCs are: CD44, CD24, CD133, ALDH1A1. Our objective was to evaluate the prognostic potential of CSC markers in HNSCC. The study included 49 patients treated for primary HNSCC, 11 patients with upper respiratory tract epithelial dysplasia and 12 subjects with the normal pharyngeal mucosa as a control group. The frequency and expression levels of the four CSC markers were assessed by immunohistochemistry. Univariate and multivariate analyses were used to correlate CSC expression levels with tumor stage, lymph node metastases or overall survival (OS). CD44, CD24, CD133, ALDH1A1 were widely expressed in tumors, whereas CD44 was found to be higher in cancer tissue (P = 0.001). ALDH1A1 expression levels were found to be significantly higher in T3-T4 tumors vs. T1-T2 tumors (P = 0.05). Lymph node metastases had significantly higher expression levels of CD24 (P = 0.01) and CD133 (P < 0.05) than primary tumors. Multifactorial analysis revealed that overall survival (OS) for patients with ALDH1A1 negative tumors was 5.25 times higher than for patients with ALDH1A1 positive (ALDH1A1+) tumors (P = 0.01). On univariate and multivariate analysis, only ALDH1A1 positivity had a significant effect on OS of HNSCC patients (HR = 2.47 for P = 0.02). Immunohistochemistry-based assessments of CSC marker expression in HNSCC has significant predictive implications for patients with HNSCC. The frequency of CSCs in the tumor, specifically of ALDH1A1+ cells correlated with five-year OS in these patients.

KEYWORDS:

CD44/CD24/CD133/ALDH1A1; Cancer stem cell; Head and neck squamous cell carcinoma; Larynx dysplasia

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